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P43136 (NR2F6_MOUSE) Reviewed, UniProtKB/Swiss-Prot

Last modified July 9, 2014. Version 123. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (2) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Interactions·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Nuclear receptor subfamily 2 group F member 6
Alternative name(s):
COUP transcription factor 3
Short name=COUP-TF3
V-erbA-related protein 2
Short name=EAR-2
Gene names
Name:Nr2f6
Synonyms:Ear-2, Ear2, Erbal2
OrganismMus musculus (Mouse) [Reference proteome]
Taxonomic identifier10090 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus

Protein attributes

Sequence length390 AA.
Sequence statusComplete.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

Transcription factor predominantly involved in transcriptional repression. Binds to promoter/enhancer response elements that contain the imperfect 5'-AGGTCA-3' direct or inverted repeats with various spacings which are also recognized by other nuclear hormone receptors. Involved in modulation of hormonal responses. Represses transcriptional activity of the lutropin-choriogonadotropic hormone receptor/LHCGR gene, the renin/REN gene and the oxytocin-neurophysin/OXT gene. Represses the triiodothyronine-dependent and -independent transcriptional activity of the thyroid hormone receptor gene in a cell type-specific manner. The corepressing function towards thyroid hormone receptor beta/THRB involves at least in part the inhibition of THRB binding to triiodothyronine response elements (TREs) by NR2F6. Inhibits NFATC transcription factor DNA binding and subsequently its transcriptional activity. Acts as transcriptional repressor of IL-17 expression in Th-17 differentiated CD4+ T cells and may be involved in induction and/or maintenance of peripheral immunological tolerance and autoimmunity. Involved in development of forebrain circadian clock; is required early in the development of the locus coeruleus (LC). Ref.8 Ref.9 Ref.11

Subunit structure

Binds DNA as dimer; homodimer and heterodimer with NR2F2 and probably NR2F1. Interacts with THRB By similarity. Ref.6 Ref.7

Subcellular location

Nucleus Ref.8.

Developmental stage

Initially expressed at E8.5 in the developing rhombencephalon. At E11.5 expression in the CNS rapidly decreases and in newborn and adult expression is not detectable in the brain with the exceptions of Purkinje neurons and the choroid plexi. Ref.9

Disruption phenotype

Reduction of neurons in the locus coerulus of the developing cortex. Defects in circadian behavior. Hyperreactive lymphocytes, late-onset immunopathology and hypersusceptibility to Th17-dependent experimental autoimmune encephalomyelitis. Ref.9 Ref.11

Sequence similarities

Belongs to the nuclear hormone receptor family. NR2 subfamily.

Contains 1 nuclear receptor DNA-binding domain.

Binary interactions

With

Entry

#Exp.

IntAct

Notes

Rasd1O356265EBI-4319956,EBI-4319979

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 390390Nuclear receptor subfamily 2 group F member 6
PRO_0000053614

Regions

DNA binding54 – 12976Nuclear receptor Ref.8
Zinc finger57 – 7721NR C4-type
Zinc finger93 – 11725NR C4-type
Region163 – 390228Ligand-binding By similarity
Region314 – 39077Important for dimerization By similarity

Amino acid modifications

Modified residue411Phosphoserine By similarity
Modified residue841Phosphoserine By similarity

Experimental info

Sequence conflict101D → G in AAA37532. Ref.2
Sequence conflict841S → T in CAA54097. Ref.1
Sequence conflict841S → T in AAA37532. Ref.2
Sequence conflict1521P → H in AAA37532. Ref.2
Sequence conflict164 – 1652QL → HV in AAA37532. Ref.2
Sequence conflict196 – 1983LLF → AV in AAA37532. Ref.2
Sequence conflict239 – 2413LPL → VAV in AAA37532. Ref.2
Sequence conflict3571Q → K in CAA54097. Ref.1

Sequences

Sequence LengthMass (Da)Tools
P43136 [UniParc].

Last modified July 27, 2011. Version 2.
Checksum: 4C30B25C6CAE5338

FASTA39041,968
        10         20         30         40         50         60 
MAMVTGGWGD PGGDTNGVDK AGGSYPRATE DDSASPPGAT SDAEPGDEER PGLQVDCVVC 

        70         80         90        100        110        120 
GDKSSGKHYG VFTCEGCKSF FKRSIRRNLS YTCRSNRDCQ IDQHHRNQCQ YCRLKKCFRV 

       130        140        150        160        170        180 
GMRKEAVQRG RIPHALPGPA ACSPPGATGV EPFTGPPVSE LIAQLLRAEP YPAAGRFGGG 

       190        200        210        220        230        240 
GAVLGIDNVC ELAARLLFST VEWARHAPFF PELPAADQVA LLRLSWSELF VLNAAQAALP 

       250        260        270        280        290        300 
LHTAPLLAAA GLHAAPMAAE RAVAFMDQVR AFQEQVDKLG RLQVDAAEYG CLKAIALFTP 

       310        320        330        340        350        360 
DACGLSDPAH VESLQEKAQV ALTEYVRAQY PSQPQRFGRL LLRLPALRAV PASLISQLFF 

       370        380        390 
MRLVGKTPIE TLIRDMLLSG STFNWPYGSG 

« Hide

References

« Hide 'large scale' references
[1]"Cloning and expression during development of three murine members of the COUP family of nuclear orphan receptors."
Jonk L.J.C., de Jonge M.E.J., Pals C.E.G.M., Wissink S., Vervaart J.M.A., Schoorlemmer J., Kruijer W.
Mech. Dev. 47:81-97(1994) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[2]"The sequence of a murine cDNA encoding Ear-2, a nuclear orphan receptor."
Barnhart K.M., Mellon P.L.
Gene 142:313-314(1994) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA].
Tissue: Pituitary.
[3]"The transcriptional landscape of the mammalian genome."
Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N., Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K., Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J. expand/collapse author list , Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R., Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T., Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A., Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B., Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M., Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S., Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E., Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D., Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M., Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H., Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V., Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S., Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H., Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N., Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F., Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G., Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z., Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C., Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y., Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S., Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K., Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R., van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H., Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M., Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C., Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S., Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K., Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M., Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C., Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A., Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.
Science 309:1559-1563(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
Strain: C57BL/6J.
[4]Mural R.J., Adams M.D., Myers E.W., Smith H.O., Venter J.C.
Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[5]"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
The MGC Project Team
Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
Strain: FVB/N.
Tissue: Mammary tumor.
[6]"Heterodimeric interactions between chicken ovalbumin upstream promoter-transcription factor family members ARP1 and ear2."
Avram D., Ishmael J.E., Nevrivy D.J., Peterson V.J., Lee S.H., Dowell P., Leid M.
J. Biol. Chem. 274:14331-14336(1999) [PubMed] [Europe PMC] [Abstract]
Cited for: SUBUNIT, INTERACTION WITH NR2F2.
[7]"Friend of GATA 2 physically interacts with chicken ovalbumin upstream promoter-TF2 (COUP-TF2) and COUP-TF3 and represses COUP-TF2-dependent activation of the atrial natriuretic factor promoter."
Huggins G.S., Bacani C.J., Boltax J., Aikawa R., Leiden J.M.
J. Biol. Chem. 276:28029-28036(2001) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH ZFPM2.
[8]"Identification of a nuclear orphan receptor (Ear2) as a negative regulator of renin gene transcription."
Liu X., Huang X., Sigmund C.D.
Circ. Res. 92:1033-1040(2003) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, DNA-BINDING, SUBCELLULAR LOCATION.
[9]"Abnormal development of the locus coeruleus in Ear2(Nr2f6)-deficient mice impairs the functionality of the forebrain clock and affects nociception."
Warnecke M., Oster H., Revelli J.P., Alvarez-Bolado G., Eichele G.
Genes Dev. 19:614-625(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, DISRUPTION PHENOTYPE, DEVELOPMENTAL STAGE.
[10]"Large-scale phosphorylation analysis of mouse liver."
Villen J., Beausoleil S.A., Gerber S.A., Gygi S.P.
Proc. Natl. Acad. Sci. U.S.A. 104:1488-1493(2007) [PubMed] [Europe PMC] [Abstract]
Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
Tissue: Liver.
[11]"The nuclear orphan receptor NR2F6 suppresses lymphocyte activation and T helper 17-dependent autoimmunity."
Hermann-Kleiter N., Gruber T., Lutz-Nicoladoni C., Thuille N., Fresser F., Labi V., Schiefermeier N., Warnecke M., Huber L., Villunger A., Eichele G., Kaminski S., Baier G.
Immunity 29:205-216(2008) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, DISRUPTION PHENOTYPE.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
X76654 mRNA. Translation: CAA54097.1.
L25674 mRNA. Translation: AAA37532.1.
AK131941 mRNA. Translation: BAE20887.1.
AK171552 mRNA. Translation: BAE42523.1.
CH466569 Genomic DNA. Translation: EDL28911.1.
BC008138 mRNA. Translation: AAH08138.1.
CCDSCCDS22392.1.
PIRS44285. I48734.
I49640.
RefSeqNP_034280.2. NM_010150.2.
UniGeneMm.28989.
Mm.440170.

3D structure databases

ProteinModelPortalP43136.
SMRP43136. Positions 55-384.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid199494. 4 interactions.
IntActP43136. 1 interaction.

PTM databases

PhosphoSiteP43136.

Proteomic databases

PaxDbP43136.
PRIDEP43136.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENSMUST00000002466; ENSMUSP00000002466; ENSMUSG00000002393.
GeneID13864.
KEGGmmu:13864.
UCSCuc009mcx.1. mouse.

Organism-specific databases

CTD2063.
MGIMGI:1352453. Nr2f6.

Phylogenomic databases

eggNOGNOG277317.
GeneTreeENSGT00720000108595.
HOGENOMHOG000260820.
HOVERGENHBG005606.
InParanoidQ922G8.
KOK08549.
OMASDMEAGD.
OrthoDBEOG72RMZ5.
TreeFamTF352097.

Gene expression databases

ArrayExpressP43136.
BgeeP43136.
CleanExMM_NR2F6.
GenevestigatorP43136.

Family and domain databases

Gene3D1.10.565.10. 1 hit.
3.30.50.10. 1 hit.
InterProIPR003068. COUP_TF.
IPR008946. Nucl_hormone_rcpt_ligand-bd.
IPR000536. Nucl_hrmn_rcpt_lig-bd_core.
IPR001723. Str_hrmn_rcpt.
IPR001628. Znf_hrmn_rcpt.
IPR013088. Znf_NHR/GATA.
[Graphical view]
PfamPF00104. Hormone_recep. 1 hit.
PF00105. zf-C4. 1 hit.
[Graphical view]
PRINTSPR01282. COUPTNFACTOR.
PR00398. STRDHORMONER.
PR00047. STROIDFINGER.
SMARTSM00430. HOLI. 1 hit.
SM00399. ZnF_C4. 1 hit.
[Graphical view]
SUPFAMSSF48508. SSF48508. 1 hit.
PROSITEPS00031. NUCLEAR_REC_DBD_1. 1 hit.
PS51030. NUCLEAR_REC_DBD_2. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

NextBio284756.
PROP43136.
SOURCESearch...

Entry information

Entry nameNR2F6_MOUSE
AccessionPrimary (citable) accession number: P43136
Secondary accession number(s): Q61504, Q922G8
Entry history
Integrated into UniProtKB/Swiss-Prot: November 1, 1995
Last sequence update: July 27, 2011
Last modified: July 9, 2014
This is version 123 of the entry and version 2 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Relevant documents

SIMILARITY comments

Index of protein domains and families

MGD cross-references

Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot